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A/CANCER DE PULMON NO CELULA PEQUEÑA (CPNCP).
A.3. TRATAMIENTO RADICAL CONCOMITANTE
En este apartado recogemos la bibliografía más importante que apoya que el tratamiento combinado de
Radioterapia (RT) torácica radical y Quimioterapia (QT) concomitante (RTQTc) es la mejor opción para
pacientes estadio III localmente avanzados considerados irresecables con buena situación funcional (PS 0-1).
Al grupo de pacientes con mala situación funcional (mayor ó igual a 2) y/ó comorbilidades asociadas no
subsidiarios de este tratamiento de RTQTc, se les debe plantear individualizadamente otras alternativas como
tratamientos secuenciales, RT exclusiva ò simplemente paliativos.
A.3.1. BENEFICIO DE TRATAMIENTO RTQTc FRENTE A TRATAMIENTO SECUENCIAL Ó RT
EXCLUSIVA:
Diversos meta-análisis, revisiones sistemáticas y estudios randomizados apoyan el tratamiento QTRTc de
inicio con Cisplatino a dosis plenas en dobletes de 2ª/3ª generación y fraccionamiento convencional de RT, a
expensas de una mayor toxicidad locoregional, fundamentalmente de esofagitis, frente a los tratamientos
secuenciales de QT de inducción y posterior RT en pacientes con buena situación funcional y respiratoria.
Previamente ya se había demostrado el beneficio del tratamiento secuencial frente a la RT exclusiva.
A.3.1.1. REVISIONES SISTEMÁTICAS Y META-ANÁLISIS:
1. Auperin A, Pechoux C, Pignon J et al. Concomitant radio-chemotherapy base on platin compounds in
patients with locally advanced non-small-cell lung cáncer (NSCLC): A meta-analysis of individual data
from 1764 patients. Ann Oncol 2006; 17:473-483. http://www.ncbi.nlm.nih.gov/pubmed/16500915
2. Auperin A, Pechoux C, Rolland E, et al. Meta-analysis of concomitant versus sequential
radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol 2010; 28(13):218190. http://www.ncbi.nlm.nih.gov/pubmed/20351327
3. H Liang, H Zhou, X Li, P Guan, B Zhou. Chemoradiotherapy for advanced non-small-cell lung cáncer:
concurrent or secuential? It’s no longer the question: a systematic review. Int J Cancer 2009;
127:718-728. http://www.ncbi.nlm.nih.gov/pubmed/19957329
4. Okawara G, Mackay JA, Evans WK, Ung YC. Management of unresected stage III non-small cell lung
cancer: a systematic review. Lung Cancer Disease Site Group of Cancer Care Ontario's Program in
Evidence-based
Care.
J
Thorac
Oncol
2006;
1(4):377.
http://www.ncbi.nlm.nih.gov/pubmed/17409887
5. O'Rourke N, RoquéI Figuls M, Farré Bernadó N, Macbeth F. Concurrent chemoradiotherapy in nonsmall
cell
lung
cancer.
OCochrane
Database
Syst
Rev
2010;
6:CD002140.
http://www.ncbi.nlm.nih.gov/pubmed/20556756
A.3.1.2. ESTUDIOS FASES III Y FASE II RANDOMIZADOS:
1
Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal
SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III
non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst 2011;
103(19):1452. http://www.ncbi.nlm.nih.gov/pubmed/21903745
2
Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase
III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin,
vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 1999;
17(9):2692. http://www.ncbi.nlm.nih.gov/pubmed/10561343
3
Fournel P, Robinet G, Thomas P, Souquet PJ, Léna H, Vergnenégre A, Delhoume JY, Le Treut J,
Silvani JA, Dansin E, Bozonnat MC, Daurés JP, Mornex F, Pérol M. Randomized phase III trial of
sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced nonsmall-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de
Pneumo-Cancérologie
NPC
95-01
Study.
http://www.ncbi.nlm.nih.gov/pubmed/16087956
J
Clin
Oncol
2005;
23(25):5910.
4
N Yamammoto, K Nakagawa, Y Nishimura, el al. Phase III study comparing second and third
generation regimens with concurrent Thoracic Radiotherapy in patients with unresectable stage III
non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol 2010;
28:3739-3745. http://www.ncbi.nlm.nih.gov/pubmed/20625120
5
Huber RM, Flentje M, Schmidt M, Pöllinger B, Gosse H, Willner J, Ulm K. Simultaneous
chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in inoperable
stage IIIA or IIIB non-small-cell lung cancer: study CTRT99/97 by the Bronchial Carcinoma Therapy
Group. J Clin Oncol 2006;24(27): 4397-404. http://www.ncbi.nlm.nih.gov/pubmed/16983107
6
EE Vokes, JE Herndon II, J Crawford, KA Leopold, MC Perry, AA Miller, MR Green. Randomized phase
II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed
by concomitant chemoradiotherapy for stage III Non-small-cell lung cancer: Cancer and Leukemia
Group
B
study
9431.
J
Clin
Oncol
2002;
20:4191-4198.
http://www.ncbi.nlm.nih.gov/pubmed/12377962
A.3.2. NO BENEFICIO DE LA CIRUGÍA EN PACIENTES N2:
Dos grandes ensayos fase III (Intergroup 0139 y EORTC 08491) no demuestran ventaja de añadir cirugía
frente a un tratamiento radical de QT/RT.
1. Albain KS, Swann RS, Rusch VW, Turrisi AT 3rd, Shepherd FA, Smith C, Chen Y, Livingston RB, Feins
RH, Gandara DR, Fry WA, Darling G, Johnson DH, Green MR, Miller RC, Ley J, Sause WT, Cox JD.
Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung
cancer:
a
phase
III
randomised
controlled
trial.
Lancet.
2009;
374(9687):379.
http://www.ncbi.nlm.nih.gov/pubmed/19632716
2. Van Meerbeeck JP, Kramer GW, Van Schil PE, Legrand C, Smit EF, Schramel F, Tjan-Heijnen VC,
Biesma B, Debruyne C, van Zandwijk N, Splinter TA, Giaccone G. Randomized controlled trial of
resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung
cancer. J Natl Cancer Inst. 2007; 99(6):442. http://www.ncbi.nlm.nih.gov/pubmed/17374834
A.3.3. NO BENEFICIO DEL TRATAMIENTO DE INDUCCION:
Tampoco se ha demostrado beneficio de la QT de inducción previa al tratamiento concomitante, ni en
estudios fase III ni en los subanálisis de las revisiones sistemáticas ó meta-análisis. Solo debe plantearse en
aquellos casos en que no sea factible la RT de inicio, por tamaño del campo de irradiación, realizándose en
todo caso un tratamiento secuencial si este es factible.
1. Vokes EE, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, Atkins JN, Watson DM,
Akerley W, Green MR. Induction chemotherapy followed by chemoradiotherapy compared with
chemoradiotherapy alone for regionally advanced unresectable stage III Non-small-cell lung cancer:
Cancer
and
Leukemia
Group
B.
J
Clin
Oncol
2007;
25(13):1698.
http://www.ncbi.nlm.nih.gov/pubmed/17404369
A.3.4. NO BENEFICIO DEL TRATAMIENTO DE CONSOLIDACIÓN:
Los dos únicos estudios publicados fase III (HOG, SWOGS0023) no demuestran beneficio ni de la QT
tipo docetaxel ni de los inhibidores de tirosina kinasa tipo gefitinib (este además produce un efecto
deletéreo).
1. Hanna N, Neubauer M, Yiannoutsos C, McGarry R, Arseneau J, Ansari R, Reynolds C, Govindan R,
Melnyk A, Fisher W, Richards D, Bruetman D, Anderson T, Chowhan N, Nattam S, Mantravadi P,
Johnson C, Breen T, White A, Einhorn L. Phase III study of cisplatin, etoposide, and concurrent chest
radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell
lung cancer: the Hoosier Oncology Group and U.S. Oncology. J Clin Oncol. 2008; 26(35):5755.
http://www.ncbi.nlm.nih.gov/pubmed/19001323
2. Kelly K, Chansky K, Gaspar LE, Albain KS, Jett J, Ung YC, Lau DH, Crowley JJ, Gandara DR. Phase III
trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel
consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol. 2008;
26(15):2450. http://www.ncbi.nlm.nih.gov/pubmed/18378568
A.3.5. BENEFICIO EN POBLACIÓN ANCIANA:
En general obtienen, si buen PS y ausencia de comorbilidades, similar beneficio a expensas de mayor
toxicidad. Lo demuestran experiencias de grupos y también los subanalisis por grupos de edad de los estudios
de revisión sistemática y meta-análisis anteriores.
1. Schild SE, Stella PJ, Geyer SM, Bonner JA, McGinnis WL, Mailliard JA, Brindle J, Jatoi A, Jett JR. The
outcome of combined-modality therapy for stage III non-small-cell lung cancer in the elderly. J Clin
Oncol. 2003;21(17):3201. http://www.ncbi.nlm.nih.gov/pubmed/12874270
2. Schild SE, Mandrekar SJ, Jatoi A, McGinnis WL, Stella PJ, Deming RL, Jett JR, Garces YI, Allen KL,
Adjei AA. The value of combined-modality therapy in elderly patients with stage III nonsmall cell lung
cancer. Cancer. 2007; 110(2):363. http://www.ncbi.nlm.nih.gov/ PMID 17542000
3. Rocha Lima CM, Herndon JE 2nd, Kosty M, Clamon G, Green MR. Therapy choices among older
patients with lung carcinoma: an evaluation of two trials of the Cancer and Leukemia Group B.
Cancer. 2002; 94(1):181. http://www.ncbi.nlm.nih.gov/pubmed/11815975
A.3.6. TUMORES DEL SULCO SUPERIOR Ó PANCOAST:
En principio debe plantearse un tratamiento de inducción de RTQTc para realizar posteriormente la
resección torácica y si esta no es factible completar el tratamiento radical de RTQTc. Los siguientes artículos
corresponden a las experiencias más importantes de grupos europeos, americanos y japoneses.
1. Kappers I, van Sandick JW, Burgers JA, Belderbos JS, Wouters MW, van Zandwijk N, Klomp HM.
Results of combined modality treatment in patients with non-small-cell lung cancer of the superior
sulcus and the rationale for surgical resection. Eur J Cardiothorac Surg 2009; 36(4):741.
http://www.ncbi.nlm.nih.gov/pubmed/19699647
2. Rusch VW, Giroux DJ, Kraut MJ, Crowley J, Hazuka M, Winton T, Johnson DH, Shulman L, Shepherd
F, Deschamps C, Livingston RB, Gandara D. Induction chemoradiation and surgical resection for
superior sulcus non-small-cell lung carcinomas: long-term results of Southwest Oncology Group Trial
9416
(Intergroup
Trial
0160).
J
Clin
Oncol.
2007;
25(3):313.
http://www.ncbi.nlm.nih.gov/pubmed/17235046
3. Kunitoh H, Kato H, Tsuboi M, Shibata T, Asamura H, Ichinose Y, Ichonose Y, Katakami N, Nagai K,
Mitsudomi T, Matsumura A, Nakagawa K, Tada H, Saijo N, Japan Clinical Oncology Group. Phase II
trial of preoperative chemoradiotherapy followed by surgical resection in patients with superior sulcus
non-small-cell lung cancers: report of Japan Clinical Oncology Group trial 9806. J Clin Oncol.
2008;26(4):644. http://www.ncbi.nlm.nih.gov/pubmed/18235125
4. Kwong KF, Edelman MJ, Suntharalingam M, Cooper LB, Gamliel Z, Burrows W, Hausner P, Doyle LA,
Krasna MJ. High-dose radiotherapy in trimodality treatment of Pancoast tumors results in high
pathologic complete response rates and excellent long-term survival. J Thorac Cardiovasc Surg. 2005;
129(6):1250. http://www.ncbi.nlm.nih.gov/pubmed/15942564
5. Pourel N, Santelmo N, Naafa N, Serre A, Hilgers W, Mineur L, Molinari N, Reboul F. Concurrent
cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus
T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response. Eur J
Cardiothorac Surg. 2008; 33(5):829. http://www.ncbi.nlm.nih.gov/pubmed/18367406